Angiogenesis, the formation of new blood vessels from existing vasculature, is known to be associated with a number of pathological conditions, including rheumatoid arthritis, diabetic retinopathy, and psoriasis, and is also an essential process for local tumour progression and the development of distant metastasis.
The formation of new capillaries is a multistep process which is controlled by positive and negative factors as well as by complex interactions between tumour cells, host endothelium, stromal cells, and extracellular matrix components. The process begins with an angiogenic stimulus to existing vasculature, usually mediated by growth factors such as vascular endothelial growth factor or basic fibroblast growth factor. This is followed by degradation of the extracellular matrix, cell adhesion changes and disruption, an increase in cell permeability, and activation of endothelial cells, e.g. proliferation of endothelial cells and their migration towards the site of blood vessel formation.
Later stages of angiogenesis include vessel lumen formation, stabilisation and differentiation by the migrating endothelial cells, basement membrane production, and the induction of vessel bed specializations. The final stages of vessel formation include what is known as remodelling, wherein a forming vasculature becomes a stable, mature vessel bed.
However, in the (normal) healthy adult, angiogenesis is virtually arrested and occurs only when needed, such as in wound healing, hair growth, renewal of the endometrium during the menstrual cycle, formation and growth of the corpus luteum during pregnancy, and in the restoration of tissue structure and function after injury.
There is therefore a need in the art to identify markers which allow endothelial cells that are participating in the process of angiogenesis (activated endothelial cells) to be distinguished from those endothelial cells which are not (quiescent endothelial cells). This is important not only for the detection of diseases or conditions associated with angiogenesis, but will allow the identification of agents that bind preferentially to activated or quiescent endothelial cells.
All references, including any patents or patent applications, cited in this specification are hereby incorporated by reference. It will be clearly understood that, although a number of prior art publications are referred to herein, this reference does not constitute an admission that any of these documents forms part of the common general knowledge in the art, in Australia or in any other country.